Di-nu-substituted piperazine derivatives and method of preparing same



Patented May 23, 1950 DI-N-SUBSTITUTED PIPERAZiNE TIVES AND METHOD OF SAME DERIVA- PREPARING John David Malkemus, Allendale, and John Ross,

Ramsey, N. J., assignors to Colgate-Palmolive- Peet Company, Jersey City, N. J a corporation of Delaware N Drawing. Application October 3, 1947,

Serial No. 777,852 Y 10 Claims. 1

This invention relates to a new class of compounds derived from heterocyclic nitrogen compounds of the type represented by piperazine and alkyl-substituted piperazines.

More particularly, the invention relates to a new class of compounds of the foregoing nature that are characterized by the presence in the molecule of (a) the ring structure of the heterocyclic nitrogen compound piperazine, (b) a long-chain aliphatic radical of from 6 to 24 carbon atoms and (0) two or more alkoxy groups of which at least one is attached to each of the two hetero-nitrogen atoms. Still more particularly, the invention relates to a new class of compounds that are derivatives of piperazine or an alkyl-substituted piperazine, further characterized by the presence of two side-chain substituents at the hetero-nitrogen atoms, one such substituent including a long-chain aliphatic radical of from 6 to 24 carbon atoms and at least one alkoxy radical, such as ethoxy, and the other side-chain substituent consisting of an alkoxy radical, such as ethoxy, the terminal oxygen atom of which is attached to a short-chainacyl or short-chain alkyl radical, the length of the short chain varying from one to three carbon atoms.

The invention further relates to a new class (if compounds having excellent foaming, deterging, wetting and lime-soap-dispersing properties.

The invention also relates to processes for preparing compounds of the foregoing nature.

It is an object of the present invention to provide a new class of compounds having enhanced surface activity for many industrial uses where surface-active compounds are required.

' It is a further object of the invention to provide a new class of compounds having surfaceactive properties characterized in that they are derivatives of a heterocyclic nitrogen compound of the class consisting of piperazine and alkylsubstituted piperazines in which one of the hetero-nitrogen atoms has attached thereto a side chain including at least one alkoxy radical, such as ethoxy, and a long-chain (C to C24) aliphatic radical, and in which the remaining hetero-nitrogen atom of the piperazine nucleus has attached thereto an alkoxy radical, such as useful as intermediates and as foaming. de-

terglng, wetting and lime-soap-dispersing agents may be obtained by suitable syntheses to be described more fully hereinafter, employing as starting materials (1) either (a) a relatively high molecular weight fatty acid (R.COOH) having from 6 to 24 carbon atoms, and preferably a fatty acid having from 12 to 18 carbon atoms, the acid being saturated or unsaturated and with or without substituents such as hydroxyl, etc., or (b) a relatively high molecular weight aliphatic halide (RX) having from 6 to 24 carbon atoms,

and preferably having from 12 to 18 carbon atoms, the aliphatic portion being saturated or unsaturated and with or without substituents such as hydroxyl, etc., (2) a convenient source of an alkoxy radical such as ethylene oxide, and (3) piperazine or an alkyl-substituted piperazine in which the alkyl substituents are preferably of not more than two carbon atoms.

The novel compounds that are obtained in accordance with the present invention in its broadest aspects fall in the class represented by the'following general structural formula:

where X is selected from the class consisting of R and R00; A and B are selected from the class consisting of unsubstituted ethylene radicals and ethylene radicals having from one to four shortchain alkyl substituents of not more than two carbon atoms each; R is a long-chain aliphatic radical such that the carbon atom content of X varies from 6 to 24 carbon atoms, and preferably from 12 to 18 carbon atoms; R is selected from the class consisting of short-chain alkyl and short-chain acyl radi'cals,'the length of the short chain varying from one to three carbon atoms; n is a small whole number varying from 1 to-9; and p is a small whole number at least 2, and preferably varying from 2 to 4.

7 A'preferred class of novel compounds within the general class set forth above is represented by those compounds containing ethoxy radicals in the side-chain substituents and having no alkyl substituents attached to any of the ring carbon atoms, and corresponding to the following general structural formula: i

' v om-o m where the various letters have the same meanings a h t immediately P e n iozmu a While the foregoing structural formulae aptly represent the general class of I compounds with which in its broadest aspects the 'presentinvention is concerned, it may also be found convenient to consider the various new compounds that;

are comprehended within th scop of thepresent invention as falling within the-following. two

sub-classes of compounds, corresponding respectively to long-chain ester and ether derivatives of piperazine or alkyl-substitute'dpiperazine, respectively. For simplicity these formulae are confined to those compounds containing ethoxy' radicals, it being understood however that alkoxy,

compounds broadly are contemplated:

In each ofthe foregoing formulae R, Rand n.

have the same meanings as before, it'being understood that R is a" long-chain aliphatic radical such that the carbon content of the entire radical (i. e., R.CO- and R-, respectively) attached to the terminal ethoxy radical varies from 6 to-24 carbonatoms, and preferably from 12 to 18 carbon atoms.

4 of any particular use or class of uses is one of the desirable features of the: present invention.

In 'makingthe long-chainfatty -acid-ester derivatives of piperazine in accordance with the present invention, a wide variety of carboxylic acids may .beemployed as starting material. For

example, suitable carboxylic acids include Iauric acid, myristic (acid; palmitic acid, stearic acid,

hydroxy-stearic acid, oleic acid, ricinoleic acid,v

lauryl s'uccinic acid, caprylic acid, isocaprylic acid, caproic acid-,- undecylenic acid, linoleic acid,

U pyl esters, etc.), may'alsof beemployed to'formthe desired long chain ester derivatives by an alcoholysis-type reaction. Also the; chlorides, bromides and iodides of-thealiphatic compounds corresponding to theseacids maybe employedin v order to provide the'corresponding ethersof the- It' will be noted that Formula Ia represents a:

long-chain fatty acidester derivative of pipera zine whereinthe long-chain acyl-radical is soparated from'the heterocyclic nitrogen ring structure by at least One ethoxy radical, whereas Forpresent invention;- to-mention only a-fewofthesuitable alkyl halides-byway of example: dodecyl; tetradecyl, hexadecyl, octadecyl, hydroxyocta decyl, AQ-oct'adecenyl (corresponding to olelyl alcohol), A9,12-octa;decadienyl (corres-pondingto mula 11) represents a long-chain aliphaticether derivative of piperazine in which the long-chain aliphatic radical is similarly separated fromlthe heterocyclic nitrogen ring structure by at least one ethoxy radical. Furthermore, in eachcase the second hetero-nitrogenatom of the piperazine nucleus carries as a substituent a shortchain' acyl or alkyl substituentof'from one'i'to three carbon atoms, the latter substituent: being separated fromthe hetero-nitrogen 'atomby a single ethoxy radical.

Before discussing suitable methods of syntheses for the compounds disclos'ed,it 'may'be well to point out at this stage of the description that thevalueof n in they preceding formulae is prefe vably s0 chosen as to'bringaabout ardesireddegree of hydrophilic and hydrophobic properties of the resulting molecule, depending .upon. the intended use for the given compound. 'In other words, it is readily possible so toadjust th value of n thatthe resulting compound will showaffinities toward both aqueous liquids; and oilyliquids. Under certain circumstances itmay be. desirable tqproduce a specif c compound- -,whose aflinit for aqueous liquidsmaterially exceeds, its affinity for oily liquids, or conversely.-v EQl-example many ore flotation processes require flotation agents .or assistantspossessing definite, properties as:. i gards, their respective 7 afiinities toward aqueous y om n nts, rdepend s'io examp e :upo factorssuch as the nature, of the ore undergoing treatment-and the particular ingredients thereof being recovered. Also in the treatment of textile materials, such'factors asthe naturezof the texof other ingredientsof; the treating; composition surface-active properties to fit the requirements linoleyl alcohol), A9,l2,15' octadecatrienyl (corresponding to linolenyl alcohol) 12"-hydroxy-A9- octa'decenyl (corresponding to ricinoleyl alcohol), hexyl, iso-octyl, etc.

The compounds according to the presentinvention maybeprepared as follows, reference being made for. the-sake of simplicity to the preparation of derivatives of piperazinecontaining-no substituents in the] heterocyclic ring-' other" than at the hetero-nitrogen atoms.

' Piperazine is reacted-With one moleculare'quiv' alent of ethylene oxide to yield monoethanol tpiperazine in accordance with the following reacion:

Ifhe monoethanol, piperazine is then reacted with ahaloalkyrether or, ester wherein the halo-v gen atom is attached. to a'sterminal carbon atom of the alkyl' radical (in e.,' in, the general case, na ctnzaon RFbeing short, chain, acyl or alkyl vgroup of flIOIIljOIlG' to three carbon .fatomsgp representing a small wholenumber varying from2' to 4, and Hal..repr esenting a halogen atomselected from the class consisting of ChIQIiHB bIOmiHG and iodine; and inthe more specific'caseunderdiscussion, with a compound having the 1 formula Hal.( 32H4.O.R.','R' and. Hal. having the same. significance as before, to, give a derivative of piperae zine .in accordance .withthe following reaction:

CHir-O'Hl:

In cases where n of the general formulae set forth above is to have a value in excess of one, the product of Equation 2 is then reacted with a further quantity of ethylene oxide gas at an elevated temperature in order to introduce a plurality of ethoXy radicals into the molecule. The reaction is preferably carried out at an elevated temperature such as the order of approximately 150 C. and under superatmospheric pressure, the particular superatmospheric pressure in any given instance being determined principally by factors such as the quantity of ethylene oxide in the system, the course of the reaction, the volume of the reaction system, and the temperature at which reaction takes place. Superatmospheric pressures autcgenously induced in the reaction system are satisfactory. In accordance with the foregoing reaction additional ethoxy radicals are introduced into the molecule as shown by the following reaction:

It will be understood that the reaction product actually obtained may contain minor amounts of the corresponding derivatives containing more and fewer ethoxy radicals respectively, the formula given however being representative of the statistical average. The reaction product thus obtained is then reacted with a long-chain fatty acid, R.COOH, in order to produce a final ester product conforming structurally to formula Ia, above:

GHz-CH:

desired, in which case the esterification of course produces also H2! and R.COOH, respectively. In case it is desired to produce the corresponding ether derivative shown in Formula 1b instead of the ester derivative of Formula Ia, then the reaction product obtained from Reaction 3 having a terminal alcoholic OH group is reacted with an alkali metal such as sodium to produce the corresponding sodyl derivative as follows:

The reaction product thus obtained is then treated with a long-chain aliphatic halide, R.X, in order to produce the desired ether compound in accordance with the following reaction:

a In general, it is ordinarily preferred to employ substantially the stoichiometric ratios of the reactants indicated by the foregoing equations. However, considerable departure from these ratios can be tolerated in many instances without serious detriment to either yields or quality of product. In connection with the reaction illustrated above as Reaction 1, however,

CHr-CH:

N.C2H4.QR' 1110 GHz-O However, instead of carrying out the esteriflca- 45 if one resorts to the use of other than substantion by means of a long-chain fatty acid, R.COOI-I, as indicated above, one may employ at this point a lower alkyl ester of the desired long-chain fatty acid, R.COO.alk., where alk. represents an alkyl radical of from one to three carbon atoms, in an 50 alcoholysis-type reaction in the presence of a small amount (varying from traces up to approximately 2% by weight of the combined reactants) of a catalyst comprising a caustic alkali, such as NaOH, this reaction proceeding as follows:

tially stoichiometric ratios of reactants it is ordinarily preferred to modify this ratio in the direction of providing an excess of piperazine, thereby decreasing the yield of undesired by-products such as diethanol piperazine. Similarly when conducting the reactions indicated above by Equations 4, 4a, 5 and 6, it is preferred to depart if at all from the use of substantially stoichiometric ratios of reactants in the direction of in- 55 suring the presence of an excess of the pipera- When R is a short-chain alkyl group, Reaction 4a takes place readily and in a straightforward manner; however when R is a short-chain acyl group, complications may be introduced in that side reactions tend to occur 'With diminution of yield of the desired product, hence it is generally preferred (when R is a short-chain acyl group) to employ other methods to obtain the unsymmetrical diester.

Alternatively, the esterification may be efiected with the use of a long-chain acid halide, R.CO.X,

oralong-chain acid anhydride, R.CO.O.OC;R.if

65 zine derivative in the reaction system. Thus ratios of about one to five mols of piperazine or piperazine derivative for each mol of other reactant in accordance with each of Reactions 1, 4, 4a., 5 and 6 represent desirable procedure in most instances.

The long-chain aliphatic ester and ether derivatives prepared according to the present invention possess very desirable surface-active properties. They are excellent detergents and are also valuable as wetting, foaming and limesoap-dispersing agents. They may be used amass the compounds of the present inventiongwhen employedin conj-unctionwith anionic suriace active- :agent's, especially in neutral or alkaline solutions, enhance considerably the d'etei' sive efl'lciencies of the latter, thus exhibiting positive synergistic action.

' The novel compounds describedh'erein exhibit desirable surface-active properties in both acid and alkaline media,-although they appear to change in character from a cationic active form to anon io'nizedmr an anionic-form, depending upon the pH of the) environment in which they are, emp1oyed.l U i The novel compounds. contemplated -as fall ing ,within the .scope of the present invention may bemadehup. in dilute-or concentrated-acme ous solution, with or without the presence of a substantial contentgof-ai low molecular weight alcohol .such as ethyl alcohol, orthey maybe made into a dry or partially; hyd'gratedsolid product, dependinguporr economical or other considerations. Adjuvant materials may be admixedwith these compounds to form flakesgr'anular particles, cakes, pastes or other physical forms of the mixture, or such adjuvant materials may be: addedto aqueous; or otherzsolutio'ns of. the compound; Such=adjuvant materials may include; sodium chloride, sodium sulphate," sodi-' um pyrophosphate as -well-uas otherbuilderS and/or fillers: employed in: the soap and synthetic detergent arts generally, care being-taken toe-avoid. the use of any additives-which would substantially.v diminish the effectiveness of the. resulting composition... Those skilled in the art will of course appreciate that the type of addition agent'to'be employed depends at'least'in part upon the ultimate-use to which the product is to be put.

7 The .properties of the specific compounds" of the. present invention .vary to some degree, de pending. upon the particular starting materials from. whichthey are prepared, butmallare'sur face-active :agents having valuable wetting, deterging, emulsifying,-- sotteningfoaming ,and limeesoap-dispersing properties. .Theyare suitablefor use as assistants in the textile and 're' lated industries where theymay- .be ernployed -for softening fabrics, fixing :colors, removing greaseandioil, .penetrating-,. etc. ,The yeare also ofz'use in the ore flotation art as addition agents to the ore treating baths employed for separating vari ous constituents of ores. V in the cosmetic industry as emulsifying agents and for stabilizing emulsions.

They are also of value! In orderto indicate even more fullythe nature havwbeenabsorbed; The resultingurea'ctlon mixture is: then::- disti11ed under substantially atiiios pheric pressure; anct thenunder reduced pre's' sure i Whileslowiy -pas'sir'rg a stream-' of an'- inert gas, such as nitro'gen; through the apparatus. About 220 parts ofmonoethanol piperazine (a viscou'soil';n5? *1.505()) are collected at -127 C-Aat anabsolute pressure of- 12 mm. of mercury;

parts of the monoethan'ol piperazine are then admixed -w-ith parts (a substantially equimolan proportion') of beta-bromoethyl-eth'yl ether "111 500 parts 'ethylealcohol' and the solution is' frefluxed forten hours. After removing: the major part of thesolvent by distillation the rest dueis made-alkaline with 10% sodiumhydroxide and then: extracted with ethyl' ether, the- 'ethyl' ether' -solutionbeing washed with small portions of I sodium: hydrox-ide'=-sdluticn and dried over potassium carbonate'r' After removing the'solve'nt by evaporation there is obtainedi'the'monoethyl ether of N,N-diethano1 piperazine having the formula:

our-om 1080 parts of this product plus' one part-sodium are then placed-in a stainless steel bomb, the air in the vessel is removed by exhaustion and replaced"with nitrogen and then the apparatus" is evacuated to' a pressureabsolute) of about 5 mm: of. mercury. I Ethylene oxide gas -is-then intermittentlyipassed intothemixture; heated to about- C. and held at this temperature fora-about 10 hour-s or" until a total of about440 parts of ethylene oxide have reacted; The-reaction-product contains a substantiatproportion of CHr-OHi Nczmooim oni ofii N ethoxy etiioxy ethanol N ethylethoxy'piper azine.

Upon reacting this last-mentioned product (at 160 -to 0., finallyunderdiminished pressure) withamixture of- 0000 fatty acidshavingan average composition represented V by the-formula CiiI-IiaCGO-Hfllai'uric-"acid?, in the ratio of 290 parts of "the former to 200parts of thelatter, there is obtained a mixture of coco fatty acid ester derivatives of piperazine correspondingin average...composition, .as. regards the numberof carbon atoms. in the fatty. acid ester-portion thereof, to the formula:

In order to produce the corresponding longchain aliphatic ether derivatives, 300 parts of C 11112:. C 0 0 .Cs 4-( 0 2114) sthe reaction product obtained according to the Example Ia procedure as a result of the introductioni'of two" molslof ethylene oxide (i. e.', the" reaction product ofi-Equation 3 where R/ is" ethyl and n. is 2) -'are' reacted with '23" parts of metallic sodium in the presence -of refluxi ng anhyd'roiis .chain alkyl chlorides corresponding to that obtained by the catalytic reduction (hydrogenation) of mixed coco fatty acids to the corresponding alcohols, followed by the conversion of the latter to the corresponding chlorides, the formula of the mixture being represented by C12H25.C1 (lauryl chloride) as regards the average composition thereof. This results in the production of the corresponding coco fatty alkyl (lauryl) ether derivatives of piperazine having the formula:

Examples [Ia and III) The procedures of Examples Ia andIb are repeated, except that the monoethanol piperazine is initially reacted with a substantially equimolar proportion of beta-bromo-ethyl acetate instead of with beta-bromoethyl-ethyl ether. The resulting products are obtained in good yields and correspond respectively to those indicated by Formulae Ia and lb above, wherein R is a C12 radical (acyl and alkyl, respectively) corresponding to the acids and alcohols derived from coco fatty acids, R is the acetyl radical, and n is 3. In these cases, therefore, the resulting compounds of Formula Ia are characterized by the presence of two terminal ester linkages (one longchain and one short-chain) while the resulting compounds of Formula ID are characterized by the presence of one terminal short-chain ester linkage and one terminal long-chain ether linkage.

In order to show typical ways in which compounds of the foregoing type may be employed, the following examples are set forth:

Example A Two parts of the coco fatty acid ester ether derivative of piperazine obtained according to the procedure of Example Ia above, are dispersed in 198 parts of water to give a 1% aqueous dispersion of the product. 1 cc. of this dispersion, when added to cc. of water, gives a turbid solution that foams well on agitation, and portions thereof added to acid and to alkaline solutions, followed by adjusting the solutions to pHs of 3.5 and 9.5, respectively, result in the production of dilute aqueous solutions which give generous quantities of foam, and which show good detersive efficiencies, when used in water having about 300 parts per million of hardness calculated as calcium carbonate. The detersive efiiciencies of these solutions are of the same order of magnitude in both acid and alkaline media; all reduce the surface tension of water markedly.

Example B One part of the lauryl polyether derivative of piperazine obtained as in Example Ib above, is dissolved in 99 parts of water to give a 1% aqueous dispersion. 1 cc. of this dispersion, when added to 10 cc. of water, yields a mixture that shows excellent foaming and detersive characteristics in both acid and alkaline solutions (pH 4.5 and 8.5, respectively), in the presence of Water showing a hardness of about 250 parts per million calculated as calcium carbonate.

Examples C and D 1% aqueous dispersions of the products obtained by the procedures of Examples 11a and III) above, when made up into aqueous solutions havnumber varying from 1 to 9.

mg. pHs of 4.0 and 9:0 display foaming and detersive characteristics that are of the same order of magnitude as those of the products of Examples Ia and lb.

While various specific examples of preferred ,ompositions and methods embodying the present invention have been described above, it will be apparent that many changes and modifications may be made in the methods of procedure and that a wide variety of specific reagents may be employed in carrying out the procedure. It should therefore be understood that the examples cited and the particular proportions, methods of procedure and compounds set forth above are intended to be illustrative only and are not in"- tended to limit the scope of the invention.

What is claimed is: 1. A piperazine derivative having the followin structural formula: Join-on,

N-O5H40.R'

ens-o where X is selected from the class consisting of Rand R.CO; R is a long-chain aliphatic radical such that the carbon atom content of X varies from 6 to 24 carbon atoms; R is selected from the class consisting of" short-chain alkyl and short-chain acyl radicals; and n is a small whole 2. A piperazine derivative havingthe followi- -ing structural formula:

where X is selected from the class consisting of R and R00; R is a long-chain aliphatic radical such that the carbon atom content of X varies from 6 to 24 carbon atoms; and R, is selected from the class consisting of short-chain alkyl and short-chain acyl radicals.

3. A piperazine derivative having the following structural formula:

where X is selected from the class consisting of R. and RCO; R is a long-chain aliphatic radical such that the carbon atom content of X varies from 6 to 24 carbon atoms; and R is selected from the class consisting of short-chain alkyl and short-chain acyl radicals, the length of the short chain varying from 1 to 3 carbon atoms.

4. A process for preparing surface-active compounds which comprises reacting (a) a compound having the following structural formula:

v-w-henefl qisaselw qd fiGm. the class consisting .of short-ohainaalkyl andi'shmh-chaim-acm radicals, the; length of ,the sghortrachaini-varyin e:fnom 1-1110 :3 h b n atem and'n1. -i, @a-wsmall wh lesnumber wvaryiii item-A .i"?Wih'=1('b) --a member of :the class -co sistin eofccarhnxyli aa ids; their low r iall lylriest lza -$heir eanhydrideseandtheir aeid halides, wherein fine carboxyliceacm I -radical rah-as from ,6 =24 carhomaboms andwecovering ,the resulting high molecular weightaester.

-1-J5-.:,A pm ess forprenarhigesuriaceeactive compounds which comprises reacting:(ahaoompound having the following-'vstructural formula:

and thereafte'r reacting 'the alkoxide'with an al- =30 kyl-ha1ide-havingfrom"6 $0 24 carbon atoms, -and recovering the resulting high mOIecuIar "weight ether.

g e 1 2 r v A -process' foi prepatingsuflaoe-axttivecompounds Whichcomprises rea'oting (a)- a compound lhavingthe following "structural formula:

the length of the short chain varying'fromiltofi carbon atoms; and n is a small whole number varying from 11709; with (b) free alkali metal to form-anaalkoxide, and thereafterwreacting'zthe aikoxide with amalkylhh'alide having from 6 to 24 carbon atOmSLand recovering the resulting high molecular weight ether;

8.:A piperazine derivative 'zaszdefinedrm' claim 3 swhereinitheacarhonzatom coniient owns 12.

;9. Amipenazine:i'ierivative-=as:defined in: .c1aima?3 swheizeingthe -carbonfiatommontenti 'OffzX'liS'L118.

110.:iA piperazinezderivativasis-definedinac1aim+3 wheneinthe carbon*atomacontent oi X is 1 6.

i 'he following references-are 'of record in ishe file of: this patent:

UNITED STATES PATENTS e-Nnmber 

1. A PIPERAZINE DERIVATIVE HAVING THE FOLLOWING STRUCTURAL FORMULA: 